Covalent organic frameworks (COFs) are a type of crystalline organic porous material with specific features and interesting structures, including porosity, large surface area, and biocompatibility. These features enable COFs to be considered as excellent candidates for applications in various fields. Recently, COFs have been widely demonstrated as promising materials for biomedical applications because of their excellent physicochemical properties and ultrathin structures. In this review, we cover the recent progress of COF materials for applications in photodynamic therapy, gene delivery, photothermal therapy, drug delivery, bioimaging, biosensing, and combined therapies. Moreover, the critical challenges and further perspectives with regards to COFs for future biology-facing applications are also discussed.